Disease relevance of Gls

• Thus AUF1 may mediate the rapid turnover of the GA mRNA, whereas increased binding of zeta-crystallin during acidosis may inhibit degradation and result in selective stabilization [1].
• Biosynthesis and processing of mitochondrial glutaminase in HTC hepatoma cells [2].
• Partial proteolysis of the fusion protein produced by a lysogen of the isolated phage generated a series of immunoreactive peptides that co-migrated with those derived from the purified brain glutaminase [3].
• (a) Presence of a prominent glutaminase activity in erythroleukemia and chloroma mitochondria is evidenced by their active glutamine-supported respiratory state 3 [4].
• Chemically-induced acidosis and alkalosis decreased (46%, p less than 0.001) and increased (24%, p less than 0.001), respectively, the activity of intestinal glutaminase, but had no effect on the colonic enzyme [5].

Psychiatry related information on Gls

• Loss of glutaminase-positive cortical neurons in Alzheimer's disease [6].

High impact information on Gls

• This study characterizes the rat ovary as a site of hormonally dependent glucose transporter (Glut) expression, and explores the potential role of interleukin (IL)-1, a putative intermediary in the ovulatory process, in this regard [7].
• Intravenously fed rats showed a simultaneous increase in glutamine utilization and a decrease in glucose utilization compared with intragastrically fed and control rats, without parallel changes in glutaminase and hexokinase activities [8].
• In contrast, glutamine use rate was 45% higher, and this was correlated with a higher maximum velocity of glutaminase in these cells [9].
• The gene coding for carbamoyl-phosphate synthetase I was formed by fusion of an ancestral glutaminase gene and a synthetase gene [10].
• In the mammalian enzyme, however, the glutaminase domain lacks a cysteine residue previously shown to interact with glutamine [10].

Chemical compound and disease context of Gls

• Despite an increase in transport, glutaminase activity was diminished and glutamine oxidation to CO2 was reduced in fibrosarcomas versus normal fibroblasts [11].
• METHODS: The authors determined proliferation rates, glutamine transport, and glutaminase activities in the human hepatoma cell lines HepG2, Huh-7, and SK-Hep, both in the presence and absence of the chemotherapeutic agents novobiocin and sodium butyrate [12].
• Treatment with NaHCO3, to correct the acidosis that accompanies diabetes, prevented the increase in renal glutaminase activity, but not that in liver or small intestine [13].
• During peripheral chemoreceptor stimulation by hypoxia (10% O2 for 30 min) or doxapram (Dox) infusion (2 mg kg-1 (30 min)-1), ventilation was recorded and successively, under the same conditions, the extracellular Glut concentration ([Glut]o) in the caudal NTS was measured by in vivo microdialysis [14].
• It is shown that Ehrlich ascites tumour cells, expressing antisense mRNA for glutaminase, contain lower levels of glutathione than normal ascites cells [15].

Biological context of Gls

• In addition, the observed kinetics established that the 71 kDa peptide is a true intermediate in the import of the mitochondrial glutaminase [2].
• However, when labelled in the presence of 5 microM-carbonyl cyanide m-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation, only a 72 kDa cytoplasmic precursor of the mitochondrial glutaminase was immunoprecipitated [2].
• A single phage was isolated from a lambda gt11 rat brain cDNA library by screening with antibodies prepared against rat renal glutaminase [3].
• This may be due to an enhanced flux caused by the elevated blood level of ammonia and an increased hydrolysis of glutamine, because of higher levels of glutaminase [16].
• Effect of acute alterations in acid-base balance on rat renal glutaminase and phosphoenolpyruvate carboxykinase gene expression [17].

Anatomical context of Gls

• Incubation of the glutaminase precursor with isolated mitochondria yields the 68- and 65-kDa peptides that are characteristic of the mature glutaminase [18].
• Expression of mitochondrial HMGCoA synthase and glutaminase in the colonic mucosa is modulated by bacterial species [19].
• Glutaminase-positive and glutaminase-negative pyramidal cells in layer VI of the primary motor and somatosensory cortices: a combined analysis by intracellular staining and immunocytochemistry in the rat [20].
• Localization of glutaminase-like and aspartate aminotransferase-like immunoreactivity in neurons of cerebral neocortex [21].
• Also, immunocytochemical study shows the presence of intense glutaminase immunoreactivity in pancreatic alpha-cells and intrapancreatic ganglia, a finding compatible with the possibility that glutamate is released from alpha-cells as well as from neurons [22].

Associations of Gls with chemical compounds

• A tetracycline-responsive promoter system was developed in LLC-PK(1)-F(+) cells to perform pulse-chase analysis of the turnover of a chimeric beta-globin (betaG) mRNA that contains 960 bp of the 3'-UTR of GA mRNA including the pH-RE [1].
• Inhibition of glutaminase reduced glutamate staining [23].
• The rate of urea production from glutamine (1 mmol/L or 10 mmol/L) in HX rats was significantly lower than that of SO rats with a concomitant decrease in hepatic glutaminase activities [24].
• Again, most dopamine neurons immunostained for glutamate; they were also immunoreactive for phosphate-activated glutaminase, the major source of neurotransmitter glutamate [23].
• Glutamate formed from glutamine by phosphate-dependent glutaminase undergoes quantitative transamination by aerobic tumor mitochondria to yield aspartate [25].

Regulatory relationships of Gls

• Significant proportions of Calb(+) (>40%) and Calret(+) (>80%) neurons were immunopositive for phosphate-activated glutaminase, the synthetic enzyme for transmitter glutamate [26].
• Administration of nerve growth factor, brain-derived neurotrophic factor and insulin-like growth factor-II protects phosphate-activated glutaminase in the ischemic and reperfused rat retinas [27].
• During CMA, SN1 expression increases five- to six-fold and appears also in cortical tubule cells in parallel with the increased expression and activity of phosphate-activated glutaminase, a mitochondrial enzyme involved in ammoniagenesis [28].
• Virtually all Nurr1-expressing neurons exhibit immunoreactivity for phosphate-activated glutaminase but not for gamma-aminobutyric acid, suggesting that they are glutamatergic-excitatory neurons [29].
• This increase in glutaminase was completely blocked by the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid, and by the NMDA receptor-linked Ca2+ ion channel blockers, MK 801 and Mg2+ [30].

Other interactions of Gls

• RNase H cleavage and Northern blot analysis of the 3'-ends established that rapid deadenylation occurred concomitantly with the rapid decay of the betaG-GA mRNA in cells grown in normal medium [1].
• The specific stimulation of NMDA receptors in PKC-depleted granule neurons or in the presence of reasonably specific PKC inhibitors also produced significant elevation in the activity of glutaminase and the expression of c-fos protein [31].
• Liver glutamine synthase activity increased by 58% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected [32].
• Arginase activity was not affected, whereas glutaminase activity was enhanced by 50% [16].
• It is suggested that, in isolated hepatocytes, BCH-induced stimulation of glucose and urea formation from glutamine results from activation of glutaminase by a mechanism which is distinct from that of glucagon [33].

Analytical, diagnostic and therapeutic context of Gls

• Subsequent gel filtration and chromatography on quaternary aminoethyl (QAE)-Sephadex and hydroxylapatite yield a 200-fold purified preparation of this glutaminase [34].
• Two-dimensional gel electrophoresis of mature GA established that the 68-kDa subunit is slightly more basic than the 66-kDa subunit [35].
• Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase [36].
• On day 24, rats were killed and studied for arterial glutamine concentration, tumor volume, kidney and gut glutaminase activity, and glutathione content (tumor, gut, heart, liver, muscle, kidney, and lung) [37].
• The extent of preservation and reperfusion injury were delineated by histologic study and by the measurement of mucosal glutaminase on tissue specimens obtained 20 min after revascularization and 24 hr and 4 weeks postoperatively [38].

References